DESCRIPTION (Applicant's abstract): In the airway, the autonomic nervous system controls smooth muscle tone, secretion by glands, and blood flow. Although there is abundant physiological and pharmacological evidence indicating that dysfunction of this autonomic control of the airways contributes to the causes and symptoms of pulmonary diseases such as bronchial asthma and emphysema, little is actually known about the regulation of these nerves. Our long term goal is to provide knowledge of how autonomic tone is regulated in the airway, especially that provided by the parasympathetic nervous system. Control of smooth muscle in the trachea and bronchi is predominantly by nerve fibers that emanate from neuronal cell bodies in parasympathetic ganglia, small clusters of cell bodies located near the airway wall. The parasympathetic tone of the airway smooth muscle is thought to be under the control of the central nervous system where signals are transmitted rhythmically during respiration to the parasympathetic neurons in the airway wall. This signal activates airway parasympathetic ganglia neurons by release of a neurotransmitter which mediates cholinergic synaptic transmission in the ganglia. A separate, but potentially important, form of neural regulation of parasympathetic neurons in the airways is by the so-called local peripheral reflex pathway. In this case, a sensory nerve is activated by changes in the airway and communicates directly with the parasympathetic neuron in the nearby ganglia by releasing neuropeptides from branches of the sensory axon, evoking non-cholinergic synaptic transmission. In other words, this is a sensory-parasympathetic reflex, independent of the central nervous system. A peripheral reflex would thus allow local increases in parasympathetic tone in an airway segment, independent of changes in another segment. This proposal describes experiments that will characterize the mechanistic basis of peripheral reflex activation of airway parasympathetic neurons in human bronchi. This will be done by: 1) measuring sensory input to individual neurons with electrophysiological and anatomical techniques and also determining the neurotransmitter that neuron synthesized; 2) identifying receptors that mediate changes in excitability during reflex activation; 3) determining the biophysical mechanisms of receptor activation, and 4) determining the effects of sensory reflex activation on smooth muscle tone.